Virtual Cell and CellML The Virtual Cell Group Center for Cell Analysis and Modeling University of Connecticut Health Center Farmington, CT – USA.

04/04/2007 CellML Workshop The Virtual Cell 2 Outline Virtual Cell – a brief introduction Current CellML support in VCell Issues Possibility of using CellML API Requirements for libCellML … Acknowledgements

04/04/2007 CellML Workshop The Virtual Cell 3 The Virtual Cell What is it?  It is a tool to build models and run simulations of cellular processes What can it do?  Modeling reactions, diffusion, membrane transport, flow, electrical potential and currents  Compartmental or spatial simulations (1D, 2D, 3D) on analytical or image-based geometries  Collaborative work (shared database) and interoperability (SBML, CellML, data formats) Where can you get it?  At What do you need to run it?  Java and an Internet connection (it runs over the web)  It is free but you must register Where can you find more info or get help?   The website (user guide, tutorials, technical info, examples) What new features are expected in the near future?  Standalone, grid-based, resource-sharing versions  Stochastics and brownian motion  Filaments and structures  Open source and plug-in architecture  Components as web services  Modeling the experiment… and much, much more!

04/04/2007 CellML Workshop The Virtual Cell 4 VCell Modeling Process Model Application (maps to experimental context) Init Condn Boundary Condn Diffusion protocols Math Description Equations Domains Sim Results time response sensitivities steady state Modeling & Analysis Structures mapped to Subdomains Subdomains (Image Regions) Structures Map reactions, fluxes, and currents Species Reactions Math Mapping Experiment External Resources pathway databases existing literature Physiological Model Cytosol ER Nucleus Extracellular A+B C D Geometry Simulation (job) Model Parameters Mesh Solver options Solver Services Fluxes Currents

04/04/2007 CellML Workshop The Virtual Cell 5 Applications Topology Geometry, Initial Conditions, Boundary Conditions, Diffusion Coefficients, Pseudo-steady, Enable/Disable Reactions Images Applications Topology Geometry, Initial Conditions, Boundary Conditions, Diffusion Coefficients, Pseudo-steady, Enable/Disable Reactions Images Applications Topology Geometry, Initial Conditions, Boundary Conditions, Diffusion Coefficients, Pseudo-steady, Enable/Disable Reactions Images Applications Topology Geometry, Initial Conditions, Boundary Conditions, Diffusion Coefficients, Pseudo-steady, Enable/Disable Reactions Electrophysiology Protocols Images Math Description VCMDL Physiology Molecular Species Compartment Topology Reactions and Fluxes Simulations Timestep, Mesh Size, Parameter Searches, Sensitivity Results Simulations Timestep, Mesh Size, Parameter Searches, Sensitivity Results Simulations Timestep, Mesh Size, Parameter Searches, Sensitivity Results

04/04/2007 CellML Workshop The Virtual Cell 6 What can we simulate? Math and Physics

04/04/2007 CellML Workshop The Virtual Cell 7 Current Scope and Future Plans Intended Users  Biologists  Biophysicists/Mathematicians Modeling domain  Compartmental or 1D, 2D, 3D Geometry  Reaction/Diffusion/Membrane Transport  Electric Potential (electrophysiology)  Advection and Membrane Diffusion Future  Optimization & parameter scans  Protocols  Advection & Directed Transport  Stochastic Processes  Complexes  Constraints & Virtual Experiments  Stand-alone & grid-based versions  Cell motility  New architecture – plug-ins, modules, etc. (VCell OpenSource)

04/04/2007 CellML Workshop The Virtual Cell 8 Current support for CellML in Virtual Cell Incomplete support for CellML  Export non-spatial biomodels and non-spatial math models to CellML1.0  Hasn’t been actively maintained Parsing of XML DOM object from CellML and translating into appropriate VCell equivalent object  Cumbersome process  Can be inconsistent Does not export electrophysiological models

04/04/2007 CellML Workshop The Virtual Cell 9 Issues to consider New Physics-oriented layer in VCell  All modeling assumptions made explicit and mathematically complete (e.g. lumped vs distributed parameter model for the same mechanism)  Components described by equations, connected to form a system (causality may be left unspecified) Compatible with CellML after determining causality (identify solvable form of equations and all state variables) VCell Physiology VCell Application New Physics Layer VCell Math Layer Solvers VCell Geometry

04/04/2007 CellML Workshop The Virtual Cell 10 Using the CellML API Using the.idl files in the CellML API package, generated the Java interface stubs Seems to provide the necessary functionality to create a CellML document Problem :  Implementation of the Java interfaces and client necessary!  Possible, but time-consuming Non-CORBA JNI (Java) Binding will be extremely helpful !!

04/04/2007 CellML Workshop The Virtual Cell 11 What do we need? …. Simple library to read, write, manipulate CellML models  similar to libSBML  we will have our own internal CellML compatible representation  With Java bindings, supporting Windows, Linux, Mac platforms  Simple methods to add/extract CellML model constructs - transparency from XML syntax Looking forward to the release of the non-CORBA JNI (Java) Binding for CellML-API (soon??) !!

04/04/2007 CellML Workshop The Virtual Cell 12 Acknowledgements We would like to thank CellML consortium for providing this opportunity to present our computational cell biology tool to the CellML community Our sincere thanks to David Nickerson for making the presentation on our behalf